Kömür Merve, Kıyan Hülya Tuba, Öztürk A Alper
Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Türkiye.
Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskişehir, Türkiye.
Sci Rep. 2025 Apr 16;15(1):13184. doi: 10.1038/s41598-025-95792-3.
In recent years, nanoparticle (NP) systems have demonstrated significant promise in pharmaceutical applications. This study focused on the development of donepezil hydrochloride-loaded PLGA-NPs, prepared using the 'Double Emulsion Solvent Evaporation' method. The impact of varying concentrations of polyvinyl alcohol-(PVA) in the aqueous phase and sonication time on NP characteristics was comprehensively examined. Results showed that increasing PVA concentration and sonication time resulted in a reduction in NP size, with an optimal formulation (I-DNP) achieving a particle size of 136.37 nm ± 0.93 and a PDI of 0.122 ± 0.011, indicating uniformity. The zeta potential was measured at - 24.17mV ± 1.21, confirming the electrostatic stability of the formulation, essential for long-term stability. Trehalose was incorporated to enhance stability, and gastrointestinal stability testing revealed that I-DNP degraded faster in acidic environments. The encapsulation efficiency reached 69.22 ± 4.84%, suggesting effective drug loading, and release studies exhibited a sustained release profile, with a Fickian and non-Fickian release mechanism. DSC, FT-IR, and H-NMR analyses confirmed the encapsulation and structural integrity of the formulation. In biological activity studies, I-DNP exhibited potent anti-AChE and anti-BuChE activities, with Chorioallantoic Membrane (CAM) assays showing significant inhibition of angiogenesis. These findings highlight the potential of I-DNP as a promising therapeutic strategy for Alzheimer's disease, demonstrating its ability to enhance drug stability, controlled release, and potential blood-brain barrier (BBB) penetration. Future studies will focus on long-term stability testing and in vivo Alzheimer's models to further validate its clinical applicability. This research contributes to the advancement of nanoparticle-based drug delivery systems for neurodegenerative diseases, paving the way for innovative therapeutic approaches.
近年来，纳米颗粒（NP）系统在药物应用中展现出了巨大的潜力。本研究聚焦于采用“复乳溶剂蒸发”法制备载盐酸多奈哌齐的聚乳酸-羟基乙酸共聚物纳米粒（PLGA-NPs）。全面考察了水相中不同浓度的聚乙烯醇（PVA）和超声处理时间对纳米粒特性的影响。结果表明，增加PVA浓度和超声处理时间会导致纳米粒尺寸减小，最佳配方（I-DNP）的粒径为136.37 nm±0.93，多分散指数（PDI）为0.122±0.011，表明具有均匀性。测得的zeta电位为-24.17 mV±1.21，证实了该配方的静电稳定性，这对长期稳定性至关重要。加入海藻糖以提高稳定性，胃肠道稳定性测试表明I-DNP在酸性环境中降解更快。包封率达到69.22±4.84%，表明药物负载有效，释放研究呈现出缓释曲线，具有菲克和非菲克释放机制。差示扫描量热法（DSC）、傅里叶变换红外光谱法（FT-IR）和氢核磁共振（H-NMR）分析证实了该配方的包封和结构完整性。在生物活性研究中，I-DNP表现出强大的抗乙酰胆碱酯酶（AChE）和抗丁酰胆碱酯酶（BuChE）活性，绒毛尿囊膜（CAM）试验显示对血管生成有显著抑制作用。这些发现突出了I-DNP作为阿尔茨海默病有前景的治疗策略的潜力，证明了其增强药物稳定性、控释以及潜在的血脑屏障（BBB）穿透能力。未来的研究将集中在长期稳定性测试和体内阿尔茨海默病模型上，以进一步验证其临床适用性。本研究为神经退行性疾病的纳米颗粒药物递送系统的发展做出了贡献，为创新治疗方法铺平了道路。
